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Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious rats.

The inhibitory effect of central administration of calcitonin-gene related peptide (CGRP) on pancreatic secretion stimulated by bile-pancreatic juice diversion was determined in conscious rats. Rats were prepared with separate cannulae for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 d after the operation without anesthesia. An injection of CGRP (1 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion as well as cholecystokinin (CCK) release induced by bile-pancreatic juice diversion. Intravenous infusion of alpha- and beta-adrenergic receptor antagonist, phentolamine and propranolol did not reverse the inhibition of pancreatic secretion. Intravenous infusion of CGRP did not affect pancreatic secretion or plasma CCK concentrations. The inhibitory action of central CGRP (i. c.v.) on pancreatic secretion and CCK release stimulated by bile-pancreatic juice diversion is partially mediated by an alpha-adrenergic mechanism, although its precise mechanism has not been elucidated.

Adrenergic alpha-Antagonists↗
PubMed2000

Mechanism of delayed gastric emptying in naturally occurring CCK-A receptor gene knockout (OLETF) rats.

We recently found a specific strain of rats (OLETF rats) in which CCK-A receptor gene expression is lacking because of a genetic abnormality. As delayed gastric emptying has been reported in this strain, we examined its mechanism. A liquid gastric load containing phenol red was administered using an orogastric tube into the stomach in OLETF and control (LETO) rats. The stomach was removed 0, 15, 30 and 45 min after meal ingestion and the content of phenol red was measured to estimate the rate of gastric emptying. Pretreatment of reserpine enhanced gastric emptying in both strains. A tenfold dose of reserpine was required in OLETF rats to induce a similar effect to LETO rats. The plasma noradrenalin level was significantly higher in OLETF than LETO rats. When the smooth muscle of the stomach was isolated and contraction in vitro was examined, the smooth muscle functions were not deteriorated in OLETF rats. The thickness of muscle determined by hematoxylin-eosin staining was not different between strains. It is suggested that the delayed gastric emptying in OLETF rats may be due to increased sympathetic nerve function.

Animals↗
PubMed2000

Distribution of geriatric disease-related genotypes in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA).

Phenotypes of various genes related to geriatric diseases and the aging process were assessed in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). The subjects were 1,297 participants in the NILS-LSA. They were community-living males and females aged 40 to 79 years who were randomly selected from the area of the NILS. Genotypic and allelic frequencies of genes in the subjects were analyzed. Age and gender differences in the distribution of genotypes were also tested. The genotypic frequencies were as follows: (1) Angiotensin I-converting enzyme (ACE) genotype was I/I 46.2%, I/D 38.3% and D/D 15.5%. (2) alpha 1-adrenoreceptor genotype was C/C 84.4%, C/T 12.7%, and T/T 3.0%. (3) Apolipoprotein E genotype was epsilon 2/epsilon 2 0%, epsilon 2/epsilon 3 7.9%, epsilon 3/epsilon 3 70.0%, epsilon 3/epsilon 4 20.8%, epsilon 2/epsilon 4 0%, and epsilon 4/epsilon 4 1.4%. (4) Cholecystokinin type-A receptor (CCKAR) nucleotide-81 (nt-81) genotype was A/A 59.1%, A/G 35.1%, and G/G 5.9%. The CCKAR nucleotide-128 genotype (nt-128) was G/G 74.3%, G/T 23.6%, and T/T 2.2%. The combination of nucleotide (nt-81, nt-128) was (A/A, G/G) 59.1%, (A/G, G/G) 14.1%, (G/G, G/G) 1.1%, (A/G, G/T) 21.0%, (G/G, G/T) 2.6%, and (G/G, T/T) 2.1%. There were no subjects with (A/A, G/T), (A/A, T/T) or (A/G, T/T) genotypic combinations. (5) beta 3-adrenoreceptor genotype was T/T 66.8%, T/A 28.5%, and A/A 4.7%. (6) Dihydrolipoamide succinyltransferase (DLST) nucleotide 19117 genotype was A/A 25.1%, A/G 49.7%, and G/G 25.1%. The DLST nucleotide 19183 genotype was C/C 55.8%, C/T 38.2%, and T/T 5.9%. The combination of nucleotide (nt19117, nt19183) was (A/A, C/C) 6.7%, (A/G, C/C) 24.1%, (G/G, C/C) 25.1%, (A/G, C/T) 25.6%, (A/A, T/T) 5.9%, and (A/A, C/T) 12.6%. There were no subjects with (A/G, T/T), (G/G, T/T) or (G/G, T/C) genotypic combinations. (7) Transforming growth factor-beta 1 genotype T/T 35.2%, T/C 44.6%, and C/C 20.2%. (8) The platelet-activating factor acetylhydrolase genotype was M/M 71.7%, M/m 27.2%, and m/m 1.2%. The mitochondria DNA 5178 genotype A was 42.1% and C was 57.9%. There were no significant gender or age differences in tested genotypic and allelic distribution except for the DLST and apolipoprotein E. Differences in the genotypic frequencies of distribution using the Hardy-Weinberg equilibrium were significant in the ACE and alpha 1-adrenoreceptor genotypes.

Adult↗
PubMed1999

Expression of cholecystokinin type A receptor gene correlates with DNA demethylation during postnatal development of rat pancreas.

Cholecystokinin stimulates pancreatic amylase secretion, gallbladder contraction, and pancreatic growth, etc. by binding with high affinity to a cholecystokinin type A receptor (CCKAR). To better understand the expression of CCKAR mRNA in terms of tissue specificity and postnatal development, we determined the methylation status of BssHII sites (5'-B sites) in the rat CCKAR gene promoter. The 5'-B sites in adult pancreas expressing CCKAR mRNA were much less extensively methylated than those in fetal pancreas not expressing the mRNA. In brain, liver, and kidney of adult rats not expressing CCKAR mRNA, the 5'-B sites were methylated. In pancreas, the demethylation level of the sites increased at 21 days after birth. Concomitant with the DNA demethylation level in the 5'-B sites, the mRNA level rose rapidly in 21 days. These results demonstrate that methylation and expression of the CCKAR gene reveal a good inverse correlation.

Animals↗
PubMed1999

Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors.

A systemic administration of cholecystokinin (CCK) increases gastric vagal afferent activity via type A CCK receptors (CCKAR). In the present study, the response of gastric vagal afferent activity to an intravenous administration of CCK was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCKAR, and compared with its control strain, Long-Evans Tokushima Otsuka (LETO) rats. The intravenous administration of 300 pmol kg(-1) and 3 nmol kg(-1) of CCK elicited dose-dependent increases in the gastric vagal afferent activity in LETO rats. The responses were not influenced by the pretreatment with L-365,260, a type B CCK receptor (CCKBR) antagonist, while they were significantly diminished by pretreatment with MK-329, a CCKAR antagonist. After pretreatment with MK-329, 3 nmol kg(-1) (but not 300 pmol kg(-1)) of CCK still elicited a small but significant increase in the activity. In the OLETF rats, both 300 pmol kg(-1) and 3 nmol kg(-1) of CCK produced small increases in the vagal afferent activity, and the responses were not influenced by pretreatment with either L-365,260 or MK-329. In addition, the systemic administration of CCK did not change gastric motility in the OLETF rats, indicating that the response of the vagal afferent activity in OLETF rats was independent of the gastric motility change. These results demonstrate that neither CCKAR nor CCKBR contributes to the response of the afferent activity of the gastric vagal nerve to a systemic administration of CCK in OLETF rats, suggesting an involvement of novel (non-A, non-B) CCK receptors.

Animals↗
PubMed1999

Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptor.

Cholecystokinin (CCK) is one of the most abundant neurotransmitter peptides in the brain. As OLETF rats lack CCK-A receptor because of a genetic abnormality, we examined whether learning and memory were impaired in these animals using an elevated eight-arm radial maze. After the completion of a radial maze study, the animals were sacrificed for histological examination of the brain. In some animals, long-term potentiation (LTP) in the hippocampus was measured. In the radial maze, the level of activity (seconds/entry) and the time remaining in the arms were significantly longer in OLETF rats. The number of errors was also significantly higher, and that of the correct choices was significantly lower in OLETF rats compared to the controls (LETO rats). The LTP of the population spike was significantly lower in the OLETF than in the LETO rats. No histological abnormalities were observed. From these observations, we concluded that learning and memory functions were impaired in the OLETF rats.

Animals↗
PubMed1999

Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

Animals↗
PubMed1999

Atropine-resistant secretion of a putative luminal CCK-releasing peptide in conscious rats.

The changes in levels of the newly discovered luminal CCK-releasing factor (LCRF) in the small intestinal lumen before and after bile-pancreatic juice diversion in conscious rats were examined by a specific RIA. Moreover, we also examined whether LCRF secretion was under cholinergic control. Anti-LCRF antiserum was raised in rabbits, and a sensitive RIA was established. The localization of LCRF was examined by immunohistochemistry. The luminal content of LCRF was significantly increased by bile-pancreatic juice diversion, during which luminal trypsin activity was eliminated. The increase in luminal LCRF content was not inhibited by intravenous infusion of atropine. The changes in plasma levels of CCK and pancreatic secretion were similar to those in luminal LCRF contents. LCRF immunostaining was observed in villus tip enterocytes of the small intestine and was most prominent in the duodenal portion. These results support our original hypothesis that LCRF may be released spontaneously into the small intestinal lumen from the villus tip enterocytes and its intraluminal degradation by proteases regulates CCK release. Furthermore, LCRF release was not subject to cholinergic regulation.

Animals↗
PubMed1999

Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.

Expressions of the cholecystokinin (CCK)-A and -B receptor genes in human duodenum, pancreas and gallbladder were examined by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. The autoradiographic study of CCK-A and -B receptors in the human duodenum and pancreas was examined in vitro. To determine the subtypes to CCK receptors in the pancreas or duodenum, we studied the abilities of CCK-A and -B receptor agonists (CCK-8 and gastrin) and antagonists (loxiglumide, L-364,718 and L-365,260) to inhibit binding of 125I-CCK-8. CCK-A receptor mRNA was not expressed in the human pancreas, but was expressed in the gallbladder and duodenum, although it was expressed in the pancreas by RT-PCR. CCK-B receptor mRNA was expressed in the pancreas, but not in gallbladder and duodenum. Using autoradiography, high concentrations of CCK-A receptors were detected in the duodenal mucosa, although in the pancreas only CCK-B receptors were detected by this method. These results suggest that localization of CCK-A receptor in human duodenum provides a biochemical and morphological basis for some physiological functions of CCK.

Autoradiography↗
PubMed1999

Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats.

The entrainment function in the suprachiasmatic nucleus (SCN) of young non-diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats was studied. OLETF rats significantly needed more days for re-entrainment to a new light-dark cycle than control Long Evans Tokushima Otsuka (LETO) rats. We also assessed Fos expression in the SCN induced by dim light exposure. The number of Fos-immunoreactive cells was significantly decreased in 5- to 13-week-old OLETF rats compared with LETO rats. Moreover, the effect of glutamate on neuronal activity in the SCN of OLETF rats were investigated. In young non-diabetic OLETF rats, the phase delay in the SCN neuronal firing rhythm induced by 1 microM glutamate was significantly less than that in LETO rats. These results suggested that the entrainment function is reduced in OLETF rats before the onset of diabetes.

Animals↗
PubMed1999

Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats.

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.

Allylglycine↗
PubMed1999

Pancreatic carcinoma associated with chronic pancreatitis.

The incidence of invasive ductal carcinoma of the pancreas was 3.1% (6 cases) in 196 patients with definite chronic pancreatitis. Five patients (3 men and 2 women) had calcific pancreatitis and 1 patient (man) had non-calcific pancreatitis. Large pancreatic stones were recognized in 2 women. Most of the patients complained of continuous intractable abdominal pain and/or back pain together with weight loss and appetite loss. Serum CA19-9 levels and exacerbation of glucose intolerance were retrospectively noted to have been elevated in 1 patient. However, it was difficult to obtain a definitive diagnosis by imaging examinations earlier, due to the presence of chronic pancreatitis. Median survival of the 6 patients was 6.5 months from admission.

Adenocarcinoma↗
PubMed1999

Gene expression of erythropoietin in renal cell carcinoma.

A 57-year-old man with renal cell carcinoma and erythrocytosis showed a high serum level of erythropoietin (EPO). High EPO signal was observed on Northern blot analysis and RT-PCR in the total RNA extracted from the renal tumor. Immunohistochemical staining also demonstrated tumor tissue with high immunostaining of EPO. Nucleotide sequences of EPO cDNA in the tumor were normal. To date, only one report has discussed the nucleotide sequences of a tumor's EPO gene; it showed mutant EPO cDNA in hepatocellular carcinoma tissue. This is the first demonstration of normal EPO cDNA in renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1999

Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: a study in CCK-B receptor gene knockout mice.

Pancreatic exocrine function and bile secretion were examined in cholecystokinin (CCK)-B receptor gene-targeted mice and compared among different genotypes [i.e., CCK-B receptor gene: (+/+), wild-type; (+/-), heterozygous; and (-/-), homozygous deficient]. The histology and protein concentrations in the pancreas also were examined. Amylase release from the dispersed acini was examined in vitro by using the various doses of CCK-8, carbachol, and secretin. In vivo, the bile and pancreatic juice were collected, and the concentrations of amylase and bile acid were measured in anesthetized mice. The responses to CCK (100 pmol/kg) or acetyl-beta-methylcholine (500 nmol/kg) were examined. In vitro studies showed that the maximal effective concentrations of CCK-8 (10(-l0) M), carbachol (10(-5) M), and secretin (5 x 10(-7) M) were comparable for all genotypes. Fluid, amylase, and bile acid outputs in vivo also were comparable for all genotypes. Pancreatic wet weight and protein concentrations were not significantly different, and no abnormal findings were observed on histologic examination in any genotype. These results indicated that the CCK-B receptor has no role in pancreatic growth, exocrine secretion, or bile secretion in adult mice.

Aging↗